1. Field of the Invention
The present invention relates to polymer complexes responsive to sugars.
The polymer complexes responsive to sugars can be utilized as a system for treating diabetes mellitus and a sugar sensor by which the release of medicines is controlled in proportion to the concentration of sugars.
2. Description of the Prior Art
Hitherto, it is known that polyvinyl alcohol is gellized by adding boric acid into an aqueous solution of a polyvinylalcohol.
Matrex PBA-30 (Trade mark, manufactured by Amicon Company, benzeneboronic acid-crosslinked agalose gel) is known as a material containing boronic acid groups in the agalose gel. It is used as a gel carrier for an affinity chromatography by using a complex which is formed by the boronic acid groups and sugars containing cis-diol groups in a buffer of pH 8.5.
Generally, in vivo in a healthy condition, homeostasis acts under good conditions. As an example, the ion concentration, the blood glucose value and the like in blood are accurately controlled by high-degree feedback systems to be kept constant. However, if the homeostasis has problems for some reason, for example, when a person contracts a chronic disease such as diabetes or hyperpiesia, regular administration of medicines such as insulin or other drugs is required according as the condition of illness. Then, the dosage and the time should be considered. Change of the homeostasis leading to cause serious consequences must be watched, especially. Hitherto, a main method for treating diabetes is a dietary treatment and self-injection in spite of the progress of medical treatment and flood of medical instruments.
Considering these problems, a system for treating diabetes having an auto-feedback system, by which a medicine is released when it is wanted and the release is stopped in normal conditions, becomes important.
Eliot et al. reported a small-sized portable apparatus which can detect the value of blood glucose by a detector of blood glucose and inject a required amount of insulin into a vein by a pump (J. Am. Med. Assoc.) 241, 223(1979).
Further, S. W. Kim disclosed a system for releasing insulin using a complex of concanavalin A and insulin modified by glucose as a molecular device having glucose sensor function and medicine release function (DIABETES, 32, 499(1983).
In other fields, it becomes important to determine glucose which is a sugar. Glucose sensors are developed in many fields such as medical treatment, food, fermentation and the like.
However, the method for gellizing polyvinyl alcohol by adding boric acid into an aqueous solution of polyvinyl alcohol is not suitable for utilizing in medical treatment because the boric acid added is toxic and the low molecules are easily diffused or permeate into materials.
The self-injection method of insulin has the following disadvantages: 1. the injection amount is different from the necessary amount, 2. the operation is troublesome, 3. there is possibility of troubles such as hypoglycemia coma, and 4. patients must have self control. It is expected to obtain a simple and safe device for controlling insulin release (artificial pancreas).
Moreover, in the method of Eliot et al., since the glucose sensor is connected with the blood stream of a patient through the skin for a long time, there are problems of infection of bacteria passing through the connection or of occurrence of a thrombus. In addition to such problems, safety and reliance of the apparatus are insufficient because there are block of a injection needle caused by crystallized insulin, troubles due to a mechanical or electronic circuit and the like. In addition, since enzyme is used in the conventional glucose sensors, there is a disadvantage of short life, namely about one week.
Further, the system of Kim et al. is prepared by dispensing the complex in a pouch made of a polymer film. When the pouch is embedded intraperitoneally, the glucose concentration increase at the outside of the pouch, an exchange reaction is occurred between insulin modified by glucose which is linked to concanavalin A and glucose, and the insulin is released. On the other hand, when the glucose concentration decreases, the exchange reaction is lowered and the release of insulin is lowered. Namely, the system is an auto-feedback system. However, since concanavalin A having very great toxicity is used in the system, there is a problem of the lack of safety.
As described above, it is desired to obtain a material releasing medicines responsive to glucose concentration which has glucose sensor function and medicine release function in a molecular device. Considering the use for pharmaceuticals, the material should have low toxicity and good formability.
Until now, the utilization of swelling of crosslinking polymer which is changed by complex formation of sugars with boronic acid groups introduced into a synthesized polymer is not reported.